Micro rna edsc350_macabali

Mignonette H. Macabali

Introduction

Brief Review of “The Central Dogma”

Cancer genes Genetic Changes in Colorectal

Cancer

The Central Dogma of Molecular Geneticsor simply “Central Dogma”Module 4, p.44 EDSC 350

http://www.nvo.com/jin/scrapbookcell/view.nhtml?profile=scrapbookcell&UID=10023

Types of Protein

Types of protein images from book Essential Cell Biology by Alberts, (2004)

Cancer Oncogenes (ex., src –

sarcoma) Proto-oncogene Activated oncogene

Tumor-suppressor gene (types, fcn.:) (ex p53 gene) Cells stop dividing Fix DNA damages induce apoptosis

Genetic changes cause normal cells to become cancerous. Credit: NCI, NIH

Genetic Changes in Colorectal Cancer

TOPIC PROPER

or “miRNAs” are small regulatory RNAs ≈22 to 26 nt in length First seen: C. elegans (Lee et al., 1993; Wightman et al.,

1993)

Also found in many other species, including flies, mice, plants, and humans

The central dogma of molecular biology suggests that the primary role of RNA is to convert the information stored in DNA into proteins.

In reality, there is much more to the RNA story.In reality, there is much more to the RNA story.Clancy, S. (2008) RNA functions. Nature Education 1(1)

http://www.nvo.com/jin/scrapbookcell/view.nhtml?profile=scrapbookcell&UID=10023

miRNA functionTypes of Protein

miRNA detection methods (1)

Northern blottingRNA

Nice to know: • Southern blotting

DNA, 1st blotting technique by Edwin Southern•Western Blotting

•Protein •Eastern Blotting

•Post-translational modifications of proteins

miRNA detection methods (2)

Quantitative Reverse Transcription – Polymerase Chain Reaction (qRT-PCR)Real Time - PCR

miRNA detection methods (3)Micro Array technique

miRNA expression profiles

Studies on miRNA function in Colorectal Cancer Asangani IA, Rasheed SA, Nikolova DA, et al. MicroRNA-21 (miR-21) post-

transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer. Oncogene 2008;27(15):2128–36.

Bandres E, Cubedo E, Agirre X, et al. Identification by real-time PCR of 13 mature microRNAs differentially expressed in colorectal cancer and non-tumoral tissues. Mol Cancer 2006;5:29.

Heneghan HM, Miller N, Lowery AJ, Sweeney KJ, Newell J, Kerin MJ. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg 2010;251(3):499–505.

Brase JC, Wuttig D, Kuner R and Sultmann H (2010). Serum microRNAs as non-invasive biomarkers for cancer Molecular Cancer 2010, 9:306

Chang KH, Mestdagh P, Vandesompele J, Kerin MJ, Miller N. Micro-RNA expression profiling to identify and validate reference genes for relative quantification in colorectal cancer. BMC Cancer 2010;10:173.

Schetter AJ, Leung SY, Sohn JJ, et al. MicroRNA expression profiles associated with prognosis and therapeutic outcome in colon adenocar- cinoma. JAMA 2008;299(4):425–36.

Other research areas for miRNA in Colorectal Cancer Fecal miRNA detection Therapeutics

Future Directions issues still need to be resolved: (1) the standard method for miRNA

quantification, (2) effective and tissue-specific delivery

method, and (3) cost-effective miRNA synthesis technique. More detailed pre-clinical and clinical studies

comparing miRNA-based diagnostics, treatments, and therapeutics with current, equivalent modalities

End of Presentation